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c‐Met identifies a population of matrix metalloproteinase 9‐producing monocytes in peritumoural stroma of hepatocellular carcinoma
Author(s) -
Zhao Lan,
Wu Yan,
Xie XuDong,
Chu YiFan,
Li JinQing,
Zheng Limin
Publication year - 2015
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.4578
Subject(s) - stroma , hepatocyte growth factor , monocyte , hepatocellular carcinoma , population , autocrine signalling , stromal cell , cancer cell , cancer research , biology , matrix metalloproteinase , immunohistochemistry , chemistry , cancer , immunology , pathology , medicine , receptor , biochemistry , environmental health
Macrophages (Mϕ) are prominent components of solid tumours and exhibit distinct phenotypes in different microenvironments. Previously, we found that tumours could alter the normal developmental process of Mϕ to trigger transient activation of monocytes in the peritumoural stroma of human hepatocellular carcinoma ( HCC ). In the present study, we showed that a fraction of monocytes in the peritumoural stroma, but not in HCC cancer nests, expressed surface c‐Met molecules. Monocytes exposed to tumours strongly expressed c‐Met proteins with kinetics similar to their activation status, and significant correlations were found between c‐Met levels and HLA‐DR expression on tumour‐infiltrating monocytes. NF‐κB ‐mediated autocrine TNF ‐α stimulated the expression of c‐Met on activated monocytes, and by interacting with its ligand hepatocyte growth factor ( HGF ), c‐Met increased the motility and matrix metalloproteinase ( MMP ) 9‐producing capacity of tumour‐associated monocytes. The intensity of c‐Met expression on tumour‐infiltrating monocytes was associated with high mortality and reduced survival of patients with HCC . Therefore, the expression of c‐Met on activated monocytes/Mϕ may represent a novel mechanism by which a tumour actively and precisely regulates the distribution and functions of these cells to facilitate disease progression. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.